Clinical Performance of the New Gore Septal Occluder in Patent Foramen Ovale Closure: A Single-Center Experience

Abstract: Background. Several progressively refined percutaneous devices for patent foramen ovale (PFO) closure have been recently developed. We describe our single-center experience with the new Gore septal occluder (GSO). Methods. Between January 2012 and May 2013, all consecutive patients with a PFO and previous cerebral thromboembolic events underwent percutaneous closure with the GSO system. Device implantation was performed under local anesthesia with combined fluoroscopic and intracardiac echographic monitoring. Follow-up schedule was: transthoracic echo at day 1 and day 30, as well as transcranial Doppler at 6 months and 12 months, all with clinical concomitant evaluation. Results. Twenty-two patients (11 males and 11 females) with a mean age of 51.2 ± 13.9 years (range, 40-74 years) had PFO closure. At baseline, 4 and 18 subjects had medium-grade and large-grade right to left permanent shunt, respectively; isolated PFO was present in 13 patients and PFO with atrial septal aneurysm was present in 9 patients. Device placement was successful in all patients. Median procedural and fluoroscopic times were 40.5 minutes (range, 22-92 minutes) and 6.5 minutes (range, 3-16 minutes), respectively. Clinical and instrumental follow-up data were obtained at 12 months in 22 patients (100%). A low-grade (<5 microbubbles) permanent residual shunt was registered in 5 patients at 6 months and in 2 patients (during Valsalva only) at 12-month follow-up. Functional PFO occlusion was thus obtained in all patients. Conclusion. This single-center initial experience suggests that the GSO is a safe and effective closure device, straightforward to implant with quick deployment and minimal imaging, and suitable for a range of atrial septal anatomies. Incidence and entity of residual shunts at follow-up were consistent with functional PFO occlusion in all patients.

J INVASIVE CARDIOL 2015;27(9):430-434

Key words: patent foramen ovale, new device, PFO closure

________________________

Patent foramen ovale (PFO) is involved in several types of disease and pathological situations.¹ Particularly, its clinical involvement in cryptogenic stroke determined a recent, significant increase in percutaneous therapeutic procedures aimed to “close the hole” in the atrial septum. Several devices have been developed and refined over time;² an optimal prosthesis should provide effective PFO closure, be simple to implant, be suitable for every anatomical situation and not interfere with other intracardiac structures, be easy to remove if required, and have a low incidence of complications. To date, the world’s most broadly used prosthesis, the Amplatzer occluder (St. Jude Medical), raises some concerns about device erosion and interference with superior vena cava and coronary sinus ostium and valvular function.^3,4 

The Gore Helex occluder (Gore Medical) is a single-wire nitinol structure covered with polytetrafluoroethylene (ePTFE) that aimed to provide greater conformability and good apposition to septal structures,⁵ but implantation procedures were reported to be difficult and closure performance was not been completely satisfactory in several series.^6-8 The structure of the new Gore septal occluder (GSO; Gore Medical) has five nitinol wires encased in a layer of ePTFE (Figure 1, upper panel), and was developed in order to simplify the implantation technique, obtaining good apposition of both discs while maintaining the atraumatic characteristic with a low device profile, and increasing the percentage of complete PFO closures.

We describe our first experience with the GSO in consecutive patients, independently of their atrial septal anatomy and/or degree of right-to-left shunt, in terms of technical performance of the device at implantation and anatomical and clinical results at mid-term follow-up.

Methods

Patient population. Between January 2012 and May 2013, all consecutive patients with an indication for PFO closure were treated using the GSO system. Indication for PFO closure was one or more documented cerebral thromboembolic event (ischemic stroke, transient ischemic attack [TIA]) related to paradoxical embolism. All patients were prospectively followed; they were treated at the department of cardiology, whereas the diagnosis of cryptogenic stroke or TIA was performed by the department of neurology or the referring neurologist. Neuroradiologic imaging (computer tomography or magnetic resonance imaging) was performed in all patients as a mandatory part of the neurological work-up. Patients were also screened for other causes of a thromboembolic event (prothrombotic coagulation diseases, for example, protein-S or protein-C deficiency, presence of atherosclerotic plaques in the extracranial arteries, the ascending aorta, or the aortic arch, or the presence of atrial fibrillation). If screening was positive, the PFO was not closed and the patient was treated medically. 

The diagnosis of right to left shunt (RLS) was initially performed by transcranial Doppler (TCD). The TCD test was performed according to a standardized procedure.⁹ In brief, 10 mL of air-mixed saline were injected into the right antecubital vein while the Doppler signal from the right middle cerebral artery during normal breathing and before a Valsalva maneuver was recorded. In cases of RLS, air microbubbles (Mb) are detected on the spectral display of the insonated artery and may be counted, allowing a quantitative assessment of the amount of shunt. When the test was positive, it was classified as low-grade shunt (1-10 Mb), medium-grade shunt (>10 Mb), large-grade shunt (>10 Mb plus a “shower” [>25 Mb]), or “curtain effect” shunt (uncountable signals).¹⁰ The shunt was also classified as permanent if already present under baseline conditions and latent when it was detected only during the Valsalva maneuver.¹¹ All patients with TCD test indicative of medium-grade or large-grade RLS underwent multiplane contrast transesophageal echocardiography (TEE) in order to confirm the anatomical site at the atrial level of the RLS and its quantification with agitated saline-contrast injection (antecubital vein) before, during, and after a Valsalva maneuver, to disclose the presence of atrial embryologic remnants (such as the Eustachian valve and/or redundant Chiari network) and to evidentiate atrial septal aneurysm (ASA). This was defined as abnormally redundant interatrial septum with an excursion of ≥10 mm into the right or left atrium and a base span of at least 15 mm.¹²

Implantation procedure. All procedures were done under fluoroscopic guidance combined with intracardiac echocardiographic (ICE) monitoring (Acunav probe connected to Acuson Cypress ultrasound machine; Siemens Medical Solutions). After local anesthesia, a bilateral venous access was gained in the femoral veins. The PFO was passed under fluoroscopic guidance with a 5 Fr multipurpose catheter (Cordis Corporation), through which a stiff guidewire was placed in the left superior pulmonary vein. The occluder device size was chosen according to the echocardiographic findings; the GSO is available in disc diameters from 15-30 mm in 5 mm increments and is preassembled and loaded onto a delivery catheter that is inserted through a short 12 Fr femoral venous sheath and advanced into the left atrium along the stiff guidewire using the preformed monorail port. Expansion of the device (left and then right atrial discs) was performed under fluoroscopy and echocardiography. At this stage, the device detaches from the delivery mandril, removing tension from the system and allowing the reach of the final positioning with the correct orientation on the atrial septum (Figure 1, lower panel). The device can be retrieved or redeployed at any stage during the delivery until it is locked to the mandril. However, after release from the mandril, a safety suture allows the device to be unlocked and removed; doing so destroys the integrity of the occluder, which cannot be reused.

Agitated saline was injected into the inferior vena cava to get baseline information about the residual shunt immediately after implantation. Successful implantation was defined as a procedural outcome that resulted in no more than a small residual shunt, with no severe complication related to the device or procedure, and no need for an additional device or surgery. After removing the femoral sheaths, hemostasis was achieved by manual compression. During the procedure, all patients were treated with 5000-7500 U of intravenous unfractionated heparin and 2000 mg of intravenous cephazolin.

Medical treatment. All patients were treated with a combined antiplatelet therapy using clopidogrel (75 mg/day) and aspirin (100 mg/day) for a period of 6 months and then with aspirin alone indefinitely. All patients were recommended for standard prophylaxis for infective endocarditis according to the guidelines of the European Society of Cardiology.

Follow-up. At 30 days post implantation, all patients underwent complete clinical evaluation with standard electrocardiogram and transthoracic echocardiogram (TTE). At 6 months, TCD with agitated saline injection was performed in an antecubital vein only, or during a complete clinical reevaluation if residual RLS was observed; at 12 months, TCD was performed during a complete clinical reevaluation in all patients. 

Statistical analysis. Data are expressed as mean ± standard deviation or median.

Results

Patients. Twenty-two patients (11 males; 11 females) with a mean age of 51.2 ± 13.9 years (range, 40-74 years) had PFO occlusion with the GSO (Table 1). Nine patients had 1 previous stroke, 2 patients >1 previous stroke, 8 patients had TIAs, and 3 patients had evidence of cerebral ischemia. Seven patients had an ASA, 2 patients had a Eustachian valve, and 1 patient had a redundant Chiari network. The entity and dynamic characteristics of the RLS are illustrated in Table 1. There was a good diagnostic correspondence between TCD and contrast TEE; TEE confirmed permanent RLS in all patients with baseline RLS at TCD, whereas RLS was less precisely quantified with TEE, particularly following the dynamic stimulus of the Valsalva maneuver. 

Procedure. Device placement was possible in all patients. Device diameters included 25 mm (n = 20), 20 mm (n = 1), and 30 mm (n = 1). The occluder was easy to successfully position in patients with simple PFO and PFO + ASA, with satisfying apposition to the atrial septum (Figure 1, lower panel). In the first patient of the series, after a successful deployment, the safety suture broke at the moment of its withdrawal. The GSO was then caught with a cardiac bioptome, recaptured into its sheath, and quite easily removed from the atrial septum; a new occluder was regularly deployed with no thromboembolic or neurological negative sequelae. In another patient, there was concern about whether the device had locked properly after deployment but before the safety suture was removed. The device was easily retrieved through its sheath and a new septal occluder was then deployed without incident. 

In all patients except the first of the series, complete closure was attained with absence of shunt on bubble contrast study from an inferior vena cava injection at the end of the procedure. Procedural and fluoroscopic mean times are reported in Table 1. Immediate procedure-related complications were not seen except for a transient, self-limiting, ST-segment elevation in inferior leads, which was probably due to a small air embolization in the right coronary artery in 1 patient. All were discharged on the day after the procedure, following clinical and femoral access-site review and cardiac TTE. 

Follow-up. Follow-up data were obtained at 12 months in all 22 patients (100%). At 30 days, 1 patient suffered from palpitations due to supraventricular ectopic beats with self-terminating, brief episodes of supraventricular tachycardia, which were well controlled with low-dose beta-blockers. Another patient had several episodes of paroxysmal atrial fibrillation subsequently controlled with flecainide 100 mg twice daily. A third patient complained of thoracic distress and migrating pain; there were no new electrocardiographic changes, no fever or signs of serositis or allergic reaction were present, and symptoms subsided with benzodiazepines. At 12 months, no patient had any clinical neurologic manifestation or deterioration in exercise capacity.

At 30 days, TTE showed all devices to be well seated with no interference with atrioventricular valves. No thrombus formation on either side of the occluder was detected. The degree of RLS during follow-up, as evaluated by TCD, is reported in Figure 2. At 6 months, 17 patients (77.3%) had no residual RLS and 5 patients (22.7%) had residual low-grade RLS during baseline conditions and during Valsalva maneuver. Of these 5 shunts, 3 disappeared at 12-month TCD and 2 remained low grade. The consequent incidence of residual low-grade RLS at 1 year post implantation was 9% (2/22); both of these residual shunts were <5 Mb, implying functional closure of PFO

Discussion

The results of PFO closure with GSO in this single-center, small series of consecutive patients can be analyzed in two main aspects: the ease of implantation and the occlusive performance of the device at mid-term follow-up.

Softness and easy adaptability to cardiac anatomic structures are two important features of an occlusive device. Gore Medical changed its device from the Gore Helex to the GSO in pursuit of a simplified implantation technique. In this regard, this series showed low procedural and fluoroscopic times that compared well with those of the most widely used device, the Amplatzer septal occluder.⁶ Since these were the first GSO implantations, and the operators had no previous experience with the precursor Helex device, a learning curve existed. This underscores the ease of positioning the GSO, as well as its safety and effectiveness. A satisfying conformability to cardiac structures was evidenced by the absence of any device malpositioning, and when necessary in 2 patients, recovery of the prosthesis was easily and rapidly achieved without any negative clinical sequelae. The 5-petal design provided good closure to the slit-like PFO structure, improving the apposition ability of the discs, as also reported by Freixa et al in a mixed group of subjects with atrial septal defect and PFO.¹³ Although the sheath size (12 Fr) was markedly bigger than the size of several competitors (in particular the Amplatzer occluder), no vascular groin complication was observed in our patients. These technical data are in complete accordance with McDonald et al,¹⁴ who described PFO closure with the GSO in 20 consecutive patients under fluoroscopy and ICE guidance. In all cases, 100% closure was attained with absence of shunt on bubble-contrast study from an inferior vena cava injection, and the device was judged suitable for a variety of atrial septal anatomies including aneurysmal septum up to 3 cm deviation and for tunnel length up to 12 mm, suggesting that the GSO is a safe, effective PFO closure device with a straightforward implantation procedure. Successful GSO deployment on the first attempt without need for retrieval was also described by Søndergaard et al in 11 patients.¹⁵ In both of these two previously reported GSO experiences, clinical follow-up was limited to 1 month in 14/20 patients¹⁴ and to a mean of 70 ± 33 days in all 11 implanted patients.¹⁵ In the initial United Kingdom experience with the GSO, reported by Thompson et al¹⁶ on 239 patients, the closure performance was mainly evaluated with bubble studies at the end of the therapeutic procedure with no systematic mid-term or long-term follow-up. In our series, 12 months of follow-up data were obtained in 100% of the study group. This allowed us to perform a mid-term evaluation of closure performance. At 6 months, no patient showed a medium-grade or large-grade residual shunt, while 5 patients (22.7%) showed a low-grade shunt (<10 Mb signals at TCD), confirming a functional closure of the PFO in all studied patients. In 3 of these 5 patients, TCD was later negative at 12-month follow-up exam, shifting from functional to complete anatomical closure. These data fit well with a report by Musto et al,¹⁷ who compared occlusion performance of GSO with the Amplatzer device, and better than the results of Thaman et al,⁶ who reported a significant residual RLS at 6 months in 32.5% of patients treated with the Amplatzer device and 58.3% of patients treated with the Gore Helex device. In these subjects, the residual RLS evaluation at follow-up was obtained by TTE, which allowed the performance of a more vigorous Valsalva maneuver than with TEE. The choice to perform a follow-up evaluation with contrast TCD in our patients, in addition to avoiding any additional semi-invasive examination, shared this objective without significant disadvantage in terms of diagnostic sensitivity.¹⁸ The 84% closure rate of the Gore Helex device at 6 months in patients described by von Bardeleben⁸ appears similar to the rate observed in our series with the GSO, but significantly better than those studies previously reporting residual RLS between 33% and 43% within 6 months^6,7 and approximately 12% at 1 year.⁸ TEE use in the evaluation of residual shunt, with less vigorous dynamic stimulation, could account for these discrepancies.

Study limitations. Our less-invasive follow-up strategy (without TEE) is one of the limitations of this study, particularly regarding the aspect of thrombus detection on the device. In this respect, TEE has been demonstrated clearly superior to TTE;¹⁹ however, thrombus formation was reported mainly on other atrial prostheses and occurred extremely rarely (0.8%) on ePTFE devices in previous large trials.^7,20 An additional limitation is the absence of a fluoroscopic evaluation of possible delayed wire fractures; these were reported in 6.4% of Gore Helex patients by Fagan et al¹⁹ and in 1.6% of GSO patients in the series by Butera et al, which shares some patients with the current report;²² however, there were no clinical sequelae. The most important predictor of wire fractures was large device size (30 mm and 35 mm); in our series, only 1 patient received a 30 mm device. Moreover, relatively small devices could favorably impact possible future erosions of cardiac structures close to the fossa ovalis; currently, there is no demonstration that GSO is safer than other devices in terms of erosions and interference with cardiac structures. Last, but not least, the number of patients studied is very small; therefore, these technical and clinical considerations have to be challenged in much larger populations and any inference on recurrence of neurological clinical events must be avoided.

Conclusion

The initial experience on this single-center, small series of consecutive patients with PFO and previous acute cerebral ischemic disease suggests that the GSO is a safe and effective closure device, straightforward to implant with quick deployment and minimal imaging, and suitable for a range of atrial septal anatomies. Mid-term follow-up results are reassuring in terms of residual shunts, but long-term GSO safety and efficacy must be evaluated over a longer follow-up period in future studies.

Acknowledgment. We greatly appreciate Mrs Daniella Engel’s editing for English language and Mr Andrea Giussani’s help providing advice and support for preparation of figures. 

References

1. Kutty S, Sengupta PP, Khandheria BK. Patent foramen ovale: the known and the to be known. J Am Coll Cardiol. 2012;59:1665-1671.
2. MacDonald ST, Carminati M, Chessa M. Managing adults with congenital heart disease in the catheterization laboratory: state of the art. Exp Rev Cardiovasc Ther. 2010;8:1741-1752.
3. El-Said HG, Moore JW. Erosion by the Amplatzer septal occluder: experienced operator opinions at odds with manufacturer recommendations? Catheter Cardiovasc Interv. 2009;73:925-930.
4. Schoen SP, Boscheri A, Lange SA, et al. Incidence of aortic valve regurgitation and outcome after percutaneous closure of atrial septal defects and patent foramen ovale. Heart. 2008;94:844-847.
5. Zahn EM, Wilson N, Cutright W, Latson LA. Development and testing of the Helex septal occluder, a new expanded polytetrafluoroethylene atrial septal defect occlusion system. Circulation. 2001;104:711-716.
6. Thaman R, Faganello G, Gimeno JR, et al. Efficacy of percutaneous closure of patent foramen ovale: comparison among three commonly used occluders. Heart. 2011;97:394-399.
7. Taaffe M, Fischer E, Baranowski A, et al. Comparison of three patent foramen ovale closure devices in a randomized trial (Amplatzer versus CardioSEAL-STARflex versus Helex occluder). Am J Cardiol. 2008;101:1353-1358.
8. von Bardeleben RS, Richter C, Otto J, et al. Long-term follow-up after percutaneous closure of PFO in 357 patients with paradoxical embolism: difference in occlusion systems and influence of atrial septum aneurysm. Int J Cardiol. 2009;134:33-41.
9. Jauss M, Zanette E. Detection of right-to-left shunt with ultrasound contrast agent and transcranial Doppler sonography. Cerebrovasc Dis. 2000;10:490-496.
10. Droste DW, Reisener M, Kemeny V, et al. Contrast transcranial Doppler ultrasound in the detection of right-to-left shunt: reproducibility, comparison of two agents, and distribution of microemboli. Stroke. 1999;30:1014-1018.
11. Angeli S, Del Sette M, Beelke M, et al. Transcranial Doppler in the diagnosis of cardiac patent foramen ovale. Neurol Sci. 2001;22:353-356. 
12. Mugge A, Daniel WG, Angermann C, et al. Atrial septal aneurysm in adult patients. A multicenter study using transthoracic and transesophageal echocardiography. Circulation. 1995;91:2785-2792.
13. Freixa X, Ibrahim R, Chan J, et al. Initial clinical experience with the Gore septal occluder for the treatment of atrial septal defects and patent foramen ovale. EuroIntervention. 2013;9:629-635. 
14. McDonald ST, Daniels MJ, Ormerod OJ. Initial use of the new Gore septal occluder in patent foramen ovale closure: implantation and preliminary results. Catheter Cardiovasc Interv. 2013;81:660-665.
15. Søndergaard L, Huan Loh P, Franzen O, et al. The first clinical experience with the new Gore septal occluder (GSO). EuroIntervention. 2013;9:959-963.
16. Thompson JD, Hildick-Smith D, Clift P, et al. Patent foramen ovale closure with the Gore septal occluder: initial UK experience. Catheter Cardiovasc Interv. 2014;83:467-473.
17. Musto C, Cifarelli A, Fiorilli R, et al. Comparison between the new Gore septal and Amplatzer devices for transcatheter closure of patent foramen ovale – short- and mid-term clinical and echocardiographic outcomes. Circ J. 2013;77:2922-2927.
18. Nemec JJ, Marwick TH, Lorig RJ, et al. Comparison of transcranial Doppler ultrasound and transesophageal contrast echocardiography in the detection of interatrial right-to-left shunts. Am J Cardiol. 1991;68:1498-1502.
19. Di Tullio MR. Patent foramen ovale: echocardiographic detection and clinical relevance in stroke. J Am Soc Echocardiogr. 2010;23:144-155.
20. Krumsdorf U, Ostermayer S, Billinger K, et al. Incidence and clinical course of thrombus formation on atrial septal defect and patent foramen ovale closure devices in 1,000 consecutive patients. J Am Coll Cardiol. 2004;43:302-309.
21. Fagan T, Dreher D, Cutright W, et al; for the Gore Helex Septal Occluder Working Group. Fracture of the Gore Helex septal occluder: associated factors and clinical outcomes. Catheter Cardiovasc Interv. 2009;73:941-948.
22. Butera GF, Saracino A, Danna P, et al. Transcatheter PFO closure with Gore septal occluder: early and mid-term clinical results. Catheter Cardiovasc Interv. 2013;82:944-949. 

____________________________

From ¹SC Cardiologia, AO Ospedale Treviglio, Treviglio (BG), Italy; and ²UO Cardiologia, Humanitas-Gavazzeni, Bergamo, Italy.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted April 2, 2014, provisional acceptance given July 7, 2014, final version accepted October 6, 2014.

Address for correspondence: Dott Paolo Sganzerla, Via Sismondi 48 20133 Milano, Italy. Email: psganzerla@alice.it